Human immunodeficiency virus type-1-specific immune responses induced by DNA vaccination are greatly enhanced by mannan-coated diC14-amidine.
Use of mannan-coated N-t-butyl-N'-tetradecyl-3-tetradecylamino-propionamidine (diC14-amidine) as an adjuvant for a DNA vaccine encoding glycoprotein 160 of human immunodeficiency virus type-1 (HIV-1) enhanced the antigen-specific immune responses. The role of interferon-gamma (IFN-gamma) and interleukin-12 in the mechanism of adjuvant action was also evaluated. Coating of diC14-amidine with mannan significantly augmented the HIV-specific delayed-type hypersensitivity reaction induced by the immunogenic DNA. HIV-1-specific cytotoxic T lymphocyte activity was also markedly enhanced by the mannan-diC14-amidine cocktail. An immunomodulatory effect of this cocktail was inhibited by treatment with anti-IFN-gamma monoclonal antibody in vivo, which suggests that IFN-gamma plays an important role in inducing cell-mediated immunity by the DNA vaccine containing this adjuvant. The results of both antigen-specific immunoglobulin isotype analysis and cytokine measurement showed that the immunogenic DNA incorporated into mannan-coated diC14-amidine elicits Th1-biased immune responses.
Sasaki
S
S
Department of Bacteriology, Yokohama City University School of Medicine, Yokohama, Japan.
Fukushima
J
J
Arai
H
H
Kusakabe
K I
KI
Hamajima
K
K
Ishii
N
N
Hirahara
F
F
Okuda
K
K
Kawamoto
S
S
Ruysschaert
J M
JM
Vandenbranden
M
M
Wahren
B
B
Okuda
K
K
D016915:AIDS Vaccines; D000578:Amidines / Q000276:immunology*; D000818:Animals; D004279:DNA, Viral / Q000276:immunology*; D005260:Female; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D016915:AIDS Vaccines; D000578:Amidines; D004279:DNA, Viral; C089665:N-t-butyl-n'-tetradecyl-3-tetradecylaminopropionamidine; D007371:Interferon-gamma